Assessing Donor-Recipient Size Mismatch in Pediatric Heart Transplantation: Lessons Learned From Over 7,500 Transplants.

BACKGROUND: To date, no studies have identified an optimal metric to match donor-recipient (D-R) pairs in pediatric heart transplantation (HT). OBJECTIVES: This study sought to identify size mismatch metrics that predicted graft survival post-HT. METHODS: D-R pairs undergoing HT in Pediatric Heart Transplant Society database from 1993 to 2021 were included. Effects of size mismatch by height, weight, body mass index, body surface area, predicted heart mass, and total cardiac volume (TCV) on 1- and 5-year graft survival and morbidity outcomes (rejection and cardiac allograft vasculopathy) were evaluated. Cox models with stepwise selection identified size metrics that independently predicted graft survival. RESULTS: Of 7,715 D-R pairs, 36.0% were well matched (D-R ratio: -20% to +20%) by weight, 39.0% by predicted heart mass, 50.0% by body surface area, 57.0% by body mass index, 71.0% by height, and 93.0% by TCV. Of all size metrics, only D-R mismatch by height and TCV predicted graft survival at 1 and 5 years. Effects of D-R size mismatch on graft survival were nonlinear. At both 1 and 5 years post-HT, D-R undersizing and oversizing by height led to increased graft loss, with graft loss observed more frequently with undersizing. Moderately undersized donors by height (D-R ratio: <-30%) frequently experienced rejection post-HT (P < 0.001). Assessing D-R size matching by TCV, minimal donor undersizing was protective, while oversizing up to 25% was not associated with increased graft loss. CONCLUSIONS: In pediatric HT, D-R appear most optimally matched using TCV. Only D-R size mismatch by TCV and height independently predicts graft survival. Standardizing size matching across centers may reduce donor discard.

Sex disparities in the current era of pediatric heart transplantation in the United States.

BACKGROUND: While sex-related differences in transplant outcomes have been well characterized amongst adults, there are no sex-specific pediatric heart transplant studies over the last decade and none evaluating waitlist outcomes. In a contemporary cohort of children undergoing heart transplantation in the United States, this analysis was performed to determine if there were sex disparities in waitlist and/or post-transplant outcomes. METHODS: Retrospective review of Scientific Registry of Transplant Recipients database from December 16, 2011 to February 28, 2019 to compare male and female children after listing and after transplant. Demographic, clinical characteristics and outcomes were compared unadjusted and after 1:1 propensity matching for selected covariates. RESULTS: Of 4089 patients, 2299 (56%) were males. At listing, males were more likely to be older, have congenital heart disease (58% vs 48%), renal dysfunction (49% vs 44%) and implantable cardioverter defibrillator (9% vs 7%). At transplant, males were more likely to have renal (42 % vs 35%) and liver dysfunction (13% vs 10%), PRA >10% (29% vs 22%) and ischemic time >3.5 hours (p < 0.05 for all). There were no significant sex differences found in unadjusted rates of transplant or mortality. After propensity matching, females had increased waitlist mortality (HR 1.3, 95%CI 1.04-1.5; p =0.019) compared to males. There were no significant differences in post-transplant morbidity or mortality (HR 1.2, 95% CI 0.93-1.5; p = 0.18) between groups. CONCLUSION: In a contemporary pediatric cohort, females have inferior heart transplant waitlist survival compared to propensity-matched males despite lower acuity of illness at listing and similar rates of transplantation. There were no sex-disparities noted in post-transplant outcomes.

Assessment of Cytomegalovirus Hybrid Preventative Strategy in Pediatric Heart Transplant Patients.

BACKGROUND: Prevention strategies for cytomegalovirus (CMV) in pediatric transplant recipients are sparsely reported. A hybrid strategy that combines prophylaxis with preemptive therapy using serial CMV viral load monitoring is an emerging option. We report our clinical outcomes with a hybrid strategy in pediatric heart transplant recipients. METHODS: A retrospective chart review was performed for pediatric heart transplant recipients who received a hybrid strategy of 2-4 weeks intravenous ganciclovir followed by serial whole blood CMV monitoring from 2002 to 2010. Subject demographics, medications, drug levels, serial CMV viral loads, intravascular ultrasound and angiography reports, and histopathology were collected. Descriptive statistics and patient groups were compared using χ(2), Fisher's exact, and Wilcoxon rank-sum tests. RESULTS: Twelve females and 13 males, ranging from 4 months to 19 years of age, underwent 26 heart transplants. Mean follow-up was 39 months (range, 5-94 months). Fourteen (54%) subjects were CMV donor (D) + /recipient (R) - , 8 (31%) were D + /R + , and 4 (15%) were D - /R + . Six subjects (23%) died of complications unrelated to CMV. Median prophylaxis duration was 25 days (range, 7-70 days). Ten (38%) subjects developed CMV infection: 1 subject had 2 episodes of CMV syndrome, and 1 subject had 2 episodes CMV. Although 6 of 14 patients with coronary artery vasculopathy had prior CMV, no association was found (P = .81). Median time to first CMV DNAemia was 2.3 months (range, 9 days to 24.8 months). Median time to viral load clearance was 29 days (range, 4-233 days). In addition, 25 D - /R- patients were transplanted and received no prophylaxis; 2 (8%) patients developed CMV infection. CONCLUSIONS: Pediatric heart transplant recipients who were at risk for CMV and treated with a novel preventative hybrid strategy developed CMV infection, syndrome, and disease at rates similar to those reported in literature for prophylactic strategies.

Quality of life in pediatric heart transplant recipients: a comparison with children with and without heart disease.

BACKGROUND: Little is known about the quality of life (QOL) of children with heart disease who undergo life-saving surgery. The aim of this multicenter study was to examine self- and parent-reported QOL outcomes in pediatric heart transplant recipients. METHODS: Pediatric heart transplant recipients/families (n = 174) from 7 transplant programs completed the Pediatric Quality of Life Inventory Generic Core Scales and Cardiac Module. Scores for the heart transplant sample were compared with non-transplant patients who had undergone conventional cardiac surgery and with a healthy child sample. Within the cardiac surgery group, heart disease/surgery was further categorized by severity/complexity. RESULTS: Heart transplant recipients were a mean age of 10.6 ± 4.7 years at a mean time post-transplant of 6.0 ± 4.1 years. By both self-report and parent proxy report, mean scores for heart transplant recipients were significantly lower than those in healthy children for physical and psychosocial QOL, including emotional and social functioning (p < 0.001), with 31.3% self-reporting significantly impaired psychosocial QOL scores. By self-report, there were no significant differences in emotional and social mean scores between the transplant and cardiac surgery groups. Transplant recipients reported significantly fewer cardiac symptoms than children with cardiac surgery (p < 0.01). Their self-reported school functioning scores were not significantly different from children with moderate to severe disease. CONCLUSION: Although pediatric heart transplant recipients experience significant symptomatic improvement, they remain at-risk for impaired psychosocial QOL, similar to children with residual or palliated heart disease. Assessment is needed to identify children at-risk and improve psychosocial outcomes.

Novel 2009 H1N1 influenza virus infection requiring extracorporeal membrane oxygenation in a pediatric heart transplant recipient.

The novel 2009 H1N1 influenza virus has been reported to have increased severity in patients with underlying cardiovascular and lung disease. Pediatric patients also appear to have an increased incidence of infection. The impact on cardiothoracic transplant recipients, especially in pediatric recipients, has not been established. We report the case of a 12-year-old boy with history of congenital heart disease who was transplanted in June 2001. In October 2009, it was found that he had developed severe acute respiratory distress syndrome (ARDS) secondary to novel 2009 H1N1 influenza virus. Extracorporeal membrane oxygenation (ECMO) was given as support. Importantly, the initial specimen evaluated by real-time reverse transcriptase-polymerase chain reaction was negative for novel 2009 H1N1 influenza virus. The patient was successfully weaned from ECMO after 24 days, extubated at 6 weeks, and continues to make steady rehabilitative progress. Early suspicion for infection and initiation of treatment, even with negative testing, is essential for cardiothoracic transplant recipients during the current pandemic of novel 2009 H1N1 influenza virus.

Safety and early outcomes using a corticosteroid-avoidance immunosuppression protocol in pediatric heart transplant recipients.

BACKGROUND: Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol. METHODS: Of the 70 patients who underwent heart transplantation during the study period, 55 eligible recipients, including 49 non-sensitized and 6 sensitized (all 55 with negative crossmatch) patients, entered a steroid-avoidance immunosuppression protocol consisting of thymoglobin induction followed by a 2-drug, tacrolimus-based, corticosteroid-free regimen. The primary outcome variable was freedom from moderate rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 2R/3A or antibody-mediated rejection). RESULTS: The median age at transplant was 7.1 years (range 2 weeks to 22 years) and median follow-up was 19 months (range 2 to 46 months). Fifty patients survived to discharge after transplantation. Of these patients, 2 (4%) were discharged on steroids and 8 (16%) started on maintenance steroids at follow-up. Rejection was diagnosed in 8 patients (Grade 2R cellular rejection in 3 and antibody-mediated rejection in 5). Freedom from rejection was 92% at 6 months (95% confidence interval [CI] 80% to 97%) and 87% at 1 year (CI 73% to 94%). Post-transplant survival was 91% at 6 months (CI 79% to 96%) and 88% at 12 and 24 months (CI 75% to 95%). There was 1 death due to rejection (antibody-mediated) 8 months after transplantation. CONCLUSIONS: An immunosuppression protocol consisting of induction followed by corticosteroid avoidance appears to achieve acceptable rejection rates during the first year post-transplant in pediatric heart transplant recipients.

Cutting balloon angioplasty for children with small-vessel pulmonary artery stenoses.

Patients with complex congenital heart disease may have pulmonary artery stenoses that are either congenital or associated with scarring following surgical procedures. This study evaluates cutting balloon angioplasty for small-vessel pulmonary artery stenoses resistant to standard balloon angioplasty. Between October 1998 and December 1999, patients were enrolled in an FDA-approved compassionate-use protocol. During four catheterizations, there were seven lesions found resistant to standard balloon angioplasty (mean lesion diameter was unchanged: 1.8 mm +/- 0.8 mm to 1.9 +/- 0.8 mm). A cutting balloon was inflated twice in each of these lesions. Standard balloon angioplasty was then repeated. Final mean lesion diameter was increased significantly (1.9 mm +/- 0.8 mm to 3.8 +/- 1.3 mm; P